Variant 11-60941260-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_016582.3(SLC15A3):c.1138G>C(p.Val380Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000638 in 1,614,028 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00031 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000038 ( 0 hom. )

Consequence

SLC15A3
NM_016582.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.20

Variant links:

Genes affected

SLC15A3 (HGNC:18068): (solute carrier family 15 member 3) Enables dipeptide transmembrane transporter activity. Involved in dipeptide import across plasma membrane. Located in intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]

SLC15A3 links:

SLC15A3 (HGNC:):

SLC15A3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10443473).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC15A3	NM_016582.3 linkuse as main transcript	c.1138G>C	p.Val380Leu	missense_variant	5/8	ENST00000227880.8	NP_057666.1	Q8IY34
SLC15A3	XM_011545095.3 linkuse as main transcript	c.1138G>C	p.Val380Leu	missense_variant	5/9		XP_011543397.1	A0A7P0T8H0
SLC15A3	NR_027391.2 linkuse as main transcript	n.1732+775G>C		intron_variant
SLC15A3	XR_007062485.1 linkuse as main transcript	n.1732+775G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC15A3	ENST00000227880.8 linkuse as main transcript	c.1138G>C	p.Val380Leu	missense_variant	5/8	1	NM_016582.3	ENSP00000227880.2		Q8IY34

Frequencies

GnomAD3 genomes

AF:

0.000309

AC:

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00106

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000996

AC:

AN:

250878

Hom.:

AF XY:

0.0000516

AC XY:

AN XY:

135610

show subpopulations

Gnomad AFR exome

AF:

0.00111

Gnomad AMR exome

AF:

0.000174

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000383

AC:

AN:

1461674

Hom.:

Cov.:

AF XY:

0.0000289

AC XY:

AN XY:

727114

show subpopulations

Gnomad4 AFR exome

AF:

0.00120

Gnomad4 AMR exome

AF:

0.000268

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000662

GnomAD4 genome

AF:

0.000308

AC:

AN:

152354

Hom.:

Cov.:

AF XY:

0.000403

AC XY:

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.00106

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000260

Hom.:

Bravo

AF:

0.000416

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000988

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 18, 2023

The c.1138G>C (p.V380L) alteration is located in exon 5 (coding exon 5) of the SLC15A3 gene. This alteration results from a G to C substitution at nucleotide position 1138, causing the valine (V) at amino acid position 380 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.66

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0083

T;.

Eigen

Benign

0.077

Eigen_PC

Benign

0.057

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.80

T;T

M_CAP

Benign

0.024

MetaRNN

Benign

0.10

T;T

MetaSVM

Benign

-0.60

MutationAssessor

Pathogenic

3.2

M;.

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-1.7

N;N

REVEL

Benign

0.13

Sift

Benign

0.060

T;T

Sift4G

Benign

0.12

T;.

Polyphen

0.64

P;.

Vest4

0.46

MVP

0.69

MPC

0.49

ClinPred

0.18

GERP RS

4.0

Varity_R

0.15

gMVP

0.53

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over